Ectopic Pregnancy (EP) is a clinical condition that occurs when the embryo implants at a site other than in the uterus, typically the fallopian tube. As the fetus grows, this condition becomes life-threatening due to potential tubal rupture and internal hemorrhage. The incidence of EP is increasing due to a number of factors, and it is now the second-most-common cause of maternal death in the first trimester of pregnancy. Nearly a third of all cases do not exhibit any clinical signs and 9% have no symptoms prior to tubal rupture.
EP is currently diagnosed using a combination of trans-vaginal ultrasound and serial detections of the biomarker, β-human chorionic gonadotrophin (β-hCG, gene name: CGB) levels, in serum. However, EP, for which there is no good experimental model system, remains difficult to diagnose at an early stage. Approximately 50% of patients with this condition initially are misdiagnosed—resulting in significant morbidity and mortality.
Efforts to diagnose EP at an early point in the pregnancy using blood tests have been hampered because of the lack of useful and reliable serum biomarkers which reliably characterize EP. Considerable difficulty in determining and identifying biomarkers for EP diagnosis has been attributed to a number of factors such as the high complexity of serum proteomes; a wide protein abundance range spanning more than 10 orders of magnitude; the presence of most clinically useful biomarkers at very low levels; a high patient-to-patient variability; and potential biases due to variations in sample collection and processing. Serum's complexity and wide dynamic range, combined with the need to detect low-abundance proteins, requires that extensive fractionation be used in order to achieve a good depth of analysis, which limits throughput. However, patient-to-patient heterogeneity requires that relatively large numbers of patient samples be analyzed.
Common compromises for dealing with these opposing factors include use of mouse or in vitro models, pooling of patient samples for the discovery phase, and/or analyzing less than ideal numbers of patients in the discovery phase followed by evaluation of candidate biomarkers in larger numbers of patients. All of these methods have not lead to a reliable early diagnostic test for EP to date.